Agonistic antibody to cd27

Abstract

The invention relates to a binding compound, which binds the same epitope of human CD27 as monoclonal antibody hCD27.15, produced by hybridoma hCD27.15 which was deposited with the ATCC in on Jun. 2, 2010 under number PTA-11008. In particular the invention relates to such a binding compound of claim 1 which may comprise: an antibody heavy chain variable region which may comprise at least one CDR selected from the group consisting of SEQ ID NOs: 5, 6 and 7, or a variant of any of said sequences; and/or an antibody light chain variable region which may comprise at least one CDR selected from the group consisting of SEQ ID NOs: 8, 9 and 10, or a variant of any of said sequences.

What is claimed is: 
     
         1 . A binding compound, which binds the same epitope of human CD27 as monoclonal antibody hCD27.15, produced by hybridoma hCD27.15 which was deposited with the ATCC on Jun. 2, 2010 under number PTA-11008. 
     
     
         2 . The binding compound of  claim 1 , comprising:
 an antibody heavy chain variable region comprising at least one CDR selected from the group consisting of SEQ ID NOs: 5, 6 and 7, or a variant of any of said sequences; and/or   an antibody light chain variable region comprising at least one CDR selected from the group consisting of SEQ ID NOs: 8, 9 and 10, or a variant of any of said sequences.   
     
     
         3 . The binding compound of  claim 1 , comprising:
 a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 3 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4.   
     
     
         4 . The binding compound of  claim 1 , which binds to CD27 and comprises:
 an antibody heavy chain variable region comprising the CDRs of SEQ ID NOs: 5, 6 and 7, or a variant of any of said sequences; and/or   an antibody light chain variable region comprising the CDRs of SEQ ID NOs: 8, 9 and 10, or a variant of any of said sequences.   
     
     
         5 . The binding compound of any one of the  claims 1 - 4 , wherein any of said variant(s) may comprise up to three amino acid modifications. 
     
     
         6 . The binding compound of  claim 1 , which compound is monoclonal antibody hCD27.15 as produced by hybridoma hCD27.15 (deposit accession number PTA-11008) or a humanized version thereof. 
     
     
         7 . The binding compound of  claim 1 , wherein the binding compound:
 binds human CD27 with a K D  of about 100 nM or lower; and   blocks binding of human CD27 to human CD70 with an IC 50  of about 10 nM or lower.   
     
     
         8 . A binding compound which competes for a binding epitope on human CD27 with any of the binding compounds of  claim 1 , and has one or more of the following characteristics:
 binds human CD27 with a K D  of about 100 nM or lower;   binds to human CD27 with about the same K D  as an antibody having a heavy chain comprising the amino acid sequence of SEQ ID NO: 3 and a light chain comprising the amino acid sequence of SEQ ID NO: 4;   blocks binding of human human CD27 to human CD70 with an IC 50  of about 10 nM or lower.   
     
     
         9 . The binding compound of  claim 1 , which is
 a chimeric antibody or a fragment thereof;   a human antibody or a fragment thereof;   a humanized antibody or a fragment thereof; or   an antibody fragment selected from the group consisting of Fab, Fab′, Fab′-SH, Fv, scFv, F(ab′) 2 , bispecific mAb and a diabody.   
     
     
         10 . An isolated polynucleotide encoding the binding compound as claimed in  claim 1 . 
     
     
         11 . Isolated polynucleotide of  claim 10 , comprising SEQ ID NOs 1 and 2, which encode the heavy and light chain of hCD27.15. 
     
     
         12 . Expression vector comprising the polynucleotide of  claim 10 . 
     
     
         13 . Host cell comprising the expression vector of  claim 11 . 
     
     
         14 . Host cell comprising the polynucleotide of  claim 10 . 
     
     
         15 . A method of producing a binding compound as claimed in  claim 1 , which method comprises:
 a) culturing host cell comprising an expression vector that comprises a polynucleotide encoding a binding compound of the invention under the control of suitable regulatory sequences in culture medium under conditions wherein the polynucleotide is expressed, thereby producing polypeptides comprising the light and heavy chain variable regions; and   b) recovering the polypeptides from the host cell or culture medium.   
     
     
         16 . Composition comprising a binding compound as claimed in  claim 1  in combination with a pharmaceutically acceptable carrier or diluent. 
     
     
         17 . Composition as claimed in  claim 16 , further comprising another active compound, in particular a therapeutically active compound, more in particular an anti-cancer drug. 
     
     
         18 . A binding compound as claimed  claim 1  for use in therapy and diagnosis. 
     
     
         19 . The binding compound as claimed in  claim 18 , wherein the therapy comprises
 stimulation of proliferation and/or survival of CD27 +  cells;   treatment of cancer; or   treatment of an autoimmune disease.   
     
     
         20 . A binding compound as claimed in  claim 1  for use in flow-cytometry, Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry.